Cancer Chemosensitivity Testing: Review
Yongzhuang Su
Cerritos, USA.
DOI: 10.4236/jct.2014.57076   PDF   HTML   XML   5,566 Downloads   7,410 Views   Citations


Since chemotherapy started in 1940s, chemosensitivity testing has been both a very attractive field and one fraught with potential pitfalls. Many methods were developed and brought initial promises, yet later ending in disappointment and were eliminated. For example, in the 1970s clonogenic assay was generally believed to be the best testing method for predicting clinical outcome. However, technical problems including low evaluation rate limited its use. Currently, MTT, ATP, DISC and Kern’s assay hold better promises. Since the 90s, the study of molecular biology has been progressing rapidly. It accelerated the understanding of molecular mechanisms of drug response. Numerous papers were published, but only few techniques can be applied in clinical practice. This review summarizes the controversies and current progress of chemosensitivity assays based on available online information, and makes a suggestion about their future routine practice.

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Su, Y. (2014) Cancer Chemosensitivity Testing: Review. Journal of Cancer Therapy, 5, 672-679. doi: 10.4236/jct.2014.57076.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Kao, S., et al. (2009) Use of Chemotherapy at End of Life in Oncology Patients. Annals of Oncology, 20, 1555-1559.
[2] Depierre, A. (2004) Pre and Perisurgical Chemotherapy of Stage I and II Resectable Non-Small Cell Lung Cancers. Revue de Pneumologie Clinique, 60, 31-36.
[3] Weisenthal, L.M. (2006) Current Status of Cell Culture Drug Resistance Testing.
[4] Blumenthal, R.D. and Goldenberg, D. (2007) Methods and Goals for the Use of in Vitro and in Vivo Chemosensitivity Testing. Molecular Biotechnology, 35, 185-197.
[5] Kern, D.H., et al. (1984) Comparison of Drug Sensitivity among Tumor Cells within a Tumor between Primary and Metastases, and between Different Metastases in the Human Tumor Colony-Forming Assay. Cancer Research, 44, 2309-2312.
[6] Ichiyoshi, Y., Endo, K., Yamamoto, M., Maehara, Y. and Sugimachi, K. (1995) Biological Features Determining the Chemosensitivity of Gastric Cancer. Human Cell, 8, 157-161.
[7] Von Hoff, D.D., Clark, G.M., et al. (1986) Simultaneous in Vitro Drug Sensitivity Testing on Tumors from Different Sites in the Same Tumor. Cancer, 58, 1007-1013.<1007::AID-CNCR2820580503>3.0.CO;2-#
[8] Phillips, R.M., Bibby, M.C. and Double, J.A. (1990) A Critical Appraisal of Predictive Value of in Vitro Chemosensitivity Assays. JNCI, 82, 1457-1468.
[9] Wu, P.H., et al. (2006) Editorial. Challenges of Chemosensitivity Testing. Clinical Cancer Research, 12, 5258.
[10] Kern, D.H., et al. (1984) Clinical Correlations with Chemosensitivities Measured in a Rapid Thymidine Incorporation Assay. Cancer Research, 44, 1725-1728.
[11] Bertelsen, C.A., Sondak, V.K., Mann, B.D., Korn, E.L. and Kern, D.H. (1984) Chemosensitivity Testing of Human Solid Tumors. A Review of 1582 Assays with 258 Clinical Correlations. Cancer, 53, 1240-1245.<1240::AID-CNCR2820530604>3.0.CO;2-Y
[12] Kurbacher, C.M., Grecu, O.M., Stier, U., Gilster, T.J., Janát, M.M., Untch, M., Konecny, G., Bruckner, H.W. and Cree, I.A. (2003) ATP Chempsensitivity Testing in Ovarian and Breast Cancer: Early Clinical Trial. Recent Results in Cancer Research, 161, 221-230.
[13] Hayon, T., et al. (2003) Appraisal of the MTT-Based Assay as a Useful Tool for Predicting Drug Chemosensitivity in Leukemia. Leukemia & Lymphoma, 44, 1957-1962.
[14] Cree, I.A. (2005) Chemosensitivity Testing Using Microplate Adenosine Triphosphate-Based Luminescence Measurements. Methods in Molecular Medicine, 110, 101-120.
[15] Sargent, J.M. (2003) The Use of the MTT Assay to Study Drug Resistance in Fresh Tumor Samples. Recent Results in Cancer Research, 161, 13-25.
[16] Weisenthal, L.M. (2011) Differential Staining Cytotoxicity Assay: A Review. Methods in Molecular Biology, 731, 259-283.
[17] Kaspers, G.J. (2005) Use of the Differential Staining Cytotoxicity Assay to Predict Chemosensitivity. Methods in Molecular Medicine, 110, 49-57.
[18] Kravisov, V.D., Greer, J.P., Whitlock, J.A. and Koury, M.J. (1998) Use of Microculture Kinetic Assay of Apoptosis in Determine Chemosensitivities of Leukemias. Blood, 92, 968-980.
[19] Brower, S.L., Fensterer, J.E. and Bush, J.E. (2008) The ChemoFx Assay: An ex Vivo Chemosensitivity and Resistance Assay for Predicting Patient Response to Cancer Chemotherapy. Methods in Molecular Biology, 414, 57-78.
[20] Masica, D.L. and Karchin, R. (2013) Collections of Simultaneously Altered Genes as Biomarkers of Cancer Cell Drug Response. Cancer Research, 73, 1699-1708.
[21] Fontaine, D., Vandenbos, F., Lebrun, C., Paquis, V. and Frenay, M. (2008) Diagnostic and Prognostic Values of 1p and 19q Deletions in Adult Gliomas: Critical Review of the Literature and Implications in Daily Clinical Practice. Revue Neurologique (Paris), 164, 595-604.
[22] Li, S., Yan, C., Huang, L., Qiu, X., Wang, Z. and Jiang, T. (2012) Molecular Prognostic Factors of Anaplastic Oligodendroglial Tumors and Its Relationship: A Single Institutional Review of 77 Patients from China. Neuro-Oncology, 14, 109-116.
[23] Wei, H.B., Hu, J., Shang, L.H., Zhang, Y.Y., Lu, F.F., Wei, M., et al. (2012) A Meta-Analytic Review of ERCC1/ MDR1 Polymorphism and Chemosensitivity to Platinum in Patients with Advanced Non-Small Cell Lung Cancer. Chinese Medical Journal (English), 125, 2902-2907.
[24] Takai, D. (2010) Aberrant Methylation of Circulating DNA for Predicting of Chemosensitivity of Non-Small Cell Lung Cancer. Gan to Kagaku Ryoho, 37, 189-193.
[25] Oda, S., Kuraoka, I. and Maehara Y. (2007) DNA Repair as a Determinant of Tumor Chemosensitivity. Gan to Kagaku Ryoho, 34, 347-357.
[26] García-Campelo, R., Alonso-Curbera, G., Aparicio, L.M.A. and Rosell, R. (2005) Pharmacogenomics in Lung Cancer: An Analysis of DNA Repair Gene Expression in Patients Treated with Platinum-Based Chemotherapy. Expert Opinion on Pharmacotherapy, 6, 2015-2026.
[27] Rosell, R., Tarón, M. and O’Brate, A. (2001) Predictive Molecular Markers in Non-Small Cell Lung Cancer. Current Opinion in Oncology, 13, 101-109.
[28] Valagussa, P. (2001) HER2 Status: A Statistician’s View. Annals of Oncology, 12, S29-S34.
[29] Scata, K.A. and El-Deiry, W.S. (2007) P53, BRCA1 and Breast Cancer Chemoresistance. Advances in Experimental Medicine and Biology, 608, 70-86.
[30] Dawood, S. (2010) Triple-Negative Breast Cancer: Epidemiology and Management Options. Drugs, 70, 2247-2258.
[31] Yasui, W. (2005) Molecular-Pathological Diagnosis of Gastric Cancer. Gan to Kagaku Ryoho, 32, 427-431.
[32] Yashi, W., Oue, N., Ito, R., Kuraoka, K. and Nakayama, H. (2004) Search for New Biomarkers of Gastric Cancer through Serial Analysis of Gene Expression and in Its Clinical Implications. Cancer Science, 95, 385-392.
[33] Sellheyer, K. and Belbin, T.J. (2004) DNA Microarrays from Structural Genomics to Functional Genomics: The Applications of Gene Chips in Dermatology and Dermatopathology. Journal of the American Academy of Dermatology, 51, 681-692.
[34] Capurso, G., Festa, S., Valente, R., Piciucchi, M., Panzuto, F., Jensen, R.T., et al. (2012) Molecular Pathology and Genetics of Pancreatic Endocrine Tumors. Journal of Molecular Endocrinology, 49, R37-R50.
[35] Almadori, G., Bussu, F. and Paludetti, G. (2008) Should There Be More Molecular Staging of Head and Neck Cancer to Improve the Choice of Treatments and Thereby Improve Survive? Current Opinion in Otolaryngology & Head & Neck Surgery, 16, 117-126.
[36] Godley, L.A., Cunningham, J., Cunningham, J., Dolan, M.E., Huang, R.S., Gurbuxani, S., McNerney, M.E., et al. (2011) An Integrated Genomic Approach to the Assessment and Treatment of Acute Myeloid Leukemia. Seminars in Oncology, 38, 215-224.
[37] Tian, C., Markman, M., Zaino, R., Ozols, R.F., McGuire, W.P., Muggia, F.M., et al. (2009) CA-125 Change after Chemotherapy in Prediction of Treatment Outcome among Advanced Mucinous and Clear Cell Epithelial Ovarian Cancers: A Gynecologic Oncology Group Study. Cancer, 115, 1395-1403.
[38] Ludwig, J.A. (2008) Personalized Therapy of Sarcomas: Integration of Biomarkers for Improved Diagnosis, Prognosis, and Therapy Selection. Current Oncology Reports, 10, 329-337.
[39] Auman, J.T., McLeod, H.L. and Akiyama, S. (2008) Cancer Pharmacogenomics, DNA Genotyping and Gene Expression Profiling to Identify Molecular Determinants of Chemosensitivity. Drug Metabolism Reviews, 40, 303-315.
[40] Huang, Y. and Sadée, W. (2003) Drug Sensitivity and Resistance Genes in Cancer Chemotherapy: A Chemogenomics Approach. Drug Discovery Today, 8, 356-363.
[41] Quintieri, L., Fantin, M. and Vizier, C. (2007) Identification of Molecular Determinants of Tumor Sensitivity and Resistance to Anticancer Drugs. Advances in Experimental Medicine and Biology, 593, 95-104.
[42] Lehne, G. (2000) P-Glycoprotein as a Drug Target in the Treatment of Multidrug Resistant Cancer. Current Drug Targets, 1, 85-99.
[43] Zhang, J.T. (2007) Use of Arrays to Investigate the Contribution of ATP-Binding Cassette Transporters to Drug Resistance in Cancer Chemotherapy and Prediction of Chemosensitivity. Cell Research, 17, 311-323.
[44] Conseil, G., Deeley, R.G. and Cole, S.P. (2005) Polymorphisms of MRP1 (ABCC1) and Related ATP-Dependent Drug Transporters. Pharmacogenetics and Genomics, 15, 523-533.
[45] Lonning, P.E. (2010) Molecular Basis for Therapy Resistance. Molecular Oncology, 4, 284-300.
[46] Kubota, T. (2000) Recent Advance in Gastric Cancer Chemotherapy. Gan to Kagaku Ryoho, 27, 2043-2047.
[47] Volpato, M. and Phillips, R.M. (2007) Tailoring Targeted Therapy to Individual Patients: Lessons to Be Learnt from the Development of Mitomycin C. Cancer Genomics & Proteomics, 4, 175-186.
[48] Bachrach, U. and Wang, Y. (2003) In Vitro Chemosensitivity Testing of Hematological Cancer Patients: Detection of Ornithire Decarboxylase. Recent Results in Cancer Research, 161, 62-70.
[49] Sita-Lumsden, A., Dart, D.A., Waxman, J. and Bevan, C.L. (2013) Circulating MicroRNAs as Potential New Biomarkers for Prostate Cancer. British Journal of Cancer, 108, 1925-1930.
[50] Pena-Llopis, S., Christie, A., Xie, X.J. and Brugarolas, J. (2013) Cooperation and Antagonism among Cancer Genes: The Renal Cancer Paradigm. Cancer Research, 73, 4173-4179.
[51] Thomas, B.H., Kjems, J. and Damgaard, C.K. (2013) Circular RNA and miR7 in Cancer. Cancer Research, 73, 5609-5612.
[52] Klaus, P. and Catherine, A.P. (2013) Real-Time Liquid Biopsy in Cancer Patients: Fact or Fiction? Cancer Research, 73, 6384-3688.
[53] Sato, H., Tsubosa, Y. and Kawano, T. (2012) Correlation between the Pretherapeutic Neutrophil to Lymphocyte Ratio and the Pathologic Response to Neoadjuvant Chemotherapy in Patients with Advanced Esophageal Cancer. World Journal of Surgery, 36, 617-622.
[54] Weber, W.A. (2006) Position Emission Tomography as an Imaging Biomarker. Journal of Clinical Oncology, 24, 3282-3292.
[55] Herrmann, K., Krause, B.J., Bundschuh, R.A., Dechow, T. and Schwaiger, M. (2009) Monitoring Response to Therapeutic Interventions in Patients with Cancer. Seminars in Nuclear Medicine, 39, 210-232.
[56] Krishan, A. and Arya, P. (2002) Monitoring of Cellular Resistance to Cancer Chemotherapy. Hematology/Oncology Clinics of North America, 16, 357-372.
[57] Katayanagi, N., Suzuki, T., Tanaka, O. and Muto, T. (1992) Flow Cytometric BrdU/DNA Assay for Anticancer Agent Sensitivity Test. Nihon Rinsho, 50, 2386-2390.
[58] Hoffman, R. (1992) Histoculture and the Immunodeficient Mouse Come to the Cancer Clinic-Rational Approches to Individualizing Cancer-Therapy and New Drug-Evaluation. International Journal of Oncology, 1, 467-474.
[59] Maenpaa, J., et al. (1988) The Subrenal Capsule Assay for Chemosensitivity Testing of Tumors. A Review. Zentralbl Gynakol, 110, 989-996.
[60] Lazaridis, G., Pentheroudakis, G. and Pavlidis, N. (2008) Integrating Trastuzumab in the Neoadjuvant Treatment of Primary Breast Cancer: Accumulating Evidence of Efficacy, Synergy and Safety. Critical Reviews in Oncology/Hematology, 66, 31-41.

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